Back to Search
Start Over
The Evolving Role of CD8+CD28− Immunosenescent T Cells in Cancer Immunology.
- Source :
- International Journal of Molecular Sciences; Jun2019, Vol. 20 Issue 11, p2810, 1p
- Publication Year :
- 2019
-
Abstract
- Functional, tumor-specific CD8<superscript>+</superscript> cytotoxic T lymphocytes drive the adaptive immune response to cancer. Thus, induction of their activity is the ultimate aim of all immunotherapies. Success of anti-tumor immunotherapy is precluded by marked immunosuppression in the tumor microenvironment (TME) leading to CD8<superscript>+</superscript> effector T cell dysfunction. Among the many facets of CD8<superscript>+</superscript> T cell dysfunction that have been recognized—tolerance, anergy, exhaustion, and senescence—CD8<superscript>+</superscript> T cell senescence is incompletely understood. Naïve CD8<superscript>+</superscript> T cells require three essential signals for activation, differentiation, and survival through T-cell receptor, costimulatory receptors, and cytokine receptors. Downregulation of costimulatory molecule CD28 is a hallmark of senescent T cells and increased CD8<superscript>+</superscript>CD28<superscript>−</superscript> senescent populations with heterogeneous roles have been observed in multiple solid and hematogenous tumors. T cell senescence can be induced by several factors including aging, telomere damage, tumor-associated stress, and regulatory T (Treg) cells. Tumor-induced T cell senescence is yet another mechanism that enables tumor cell resistance to immunotherapy. In this paper, we provide a comprehensive overview of CD8<superscript>+</superscript>CD28<superscript>−</superscript> senescent T cell population, their origin, their function in immunology and pathologic conditions, including TME and their implication for immunotherapy. Further characterization and investigation into this subset of CD8<superscript>+</superscript> T cells could improve the efficacy of future anti-tumor immunotherapy. [ABSTRACT FROM AUTHOR]
- Subjects :
- TELOMERES
T cells
CYTOTOXIC T cells
CANCER cells
CELLULAR aging
CYTOKINE receptors
Subjects
Details
- Language :
- English
- ISSN :
- 16616596
- Volume :
- 20
- Issue :
- 11
- Database :
- Complementary Index
- Journal :
- International Journal of Molecular Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 137037167
- Full Text :
- https://doi.org/10.3390/ijms20112810